(R)-4-(3,4-difluorophenyl)-3-(((R)-1-phenylethyl)amino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)butan-1-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-4-(3,4-difluorophenyl)-3-(((R)-1-phenylethyl)amino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)butan-1-one
• 英文别名: (3R)-4-(3,4-difluorophenyl)-3-[[(1R)-1-phenylethyl]amino]-1-[3-(trifluoromethyl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]butan-1-one
• 化学式: C₂₄H₂₄F₅N₅O
• 分子量: 493.479
• InChiKey: RSPQDCIMWWCJCH-CRAIPNDOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3,4-二氟苯乙酸 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 甲烷磺酸 、 三甲基乙酰氯 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 乙酸乙酯 、 异丙醇 、 甲苯 为溶剂， 生成 (R)-4-(3,4-difluorophenyl)-3-(((R)-1-phenylethyl)amino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)butan-1-one 、 (S)-4-(3,4-difluorophenyl)-3-(((R)-1-phenylethyl)amino)-1-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)butan-1-one
  参考文献：
  名称：

  Practical, Asymmetric Route to Sitagliptin and Derivatives: Development and Origin of Diastereoselectivity

  摘要：

  The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S=O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H center dot center dot center dot F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.

  DOI：

  10.1021/acs.orglett.5b00520

文献信息

• PROCESS FOR THE PREPARATION OF CHIRAL BETA AMINO CARBOXAMIDE DERIVATIVES
  申请人：Jadav Kanaksinh Jesingbhai

  公开号：US20130041150A1

  公开（公告）日：2013-02-14

  The present invention provides a process for preparing a compound of formula (I), or a pharmaceutically acceptable salt thereof, having the R-configuration, of formula (IA), or S-configuration of formula (IB), selectively over the other enantiomer.

  本发明提供了一种制备式(I)化合物或其药学上可接受的盐的过程，该化合物具有R构型的式(IA)或S构型的式(IB)，并且能够选择性地制备其中一种对映异构体，而不是另一种对映异构体。
• US8471016B2
  申请人：——

  公开号：US8471016B2

  公开（公告）日：2013-06-25
• Practical, Asymmetric Route to Sitagliptin and Derivatives: Development and Origin of Diastereoselectivity
  作者：Osvaldo Gutierrez、Dattatray Metil、Namrata Dwivedi、Nagaraju Gudimalla、E. R. R. Chandrashekar、Vilas H. Dahanukar、Apurba Bhattacharya、Rakeshwar Bandichhor、Marisa C. Kozlowski

  DOI：10.1021/acs.orglett.5b00520

  日期：2015.4.3

  The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S=O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H center dot center dot center dot F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.